Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19105 | 57538;57539;57540 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| N2AB | 17464 | 52615;52616;52617 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| N2A | 16537 | 49834;49835;49836 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| N2B | 10040 | 30343;30344;30345 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| Novex-1 | 10165 | 30718;30719;30720 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| Novex-2 | 10232 | 30919;30920;30921 | chr2:178597769;178597768;178597767 | chr2:179462496;179462495;179462494 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/L | rs1450682516  |
None | 1.0 | N | 0.722 | 0.468 | 0.610363733556 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/L | rs1450682516 |
None | 1.0 | N | 0.722 | 0.468 | 0.610363733556 | gnomAD-4.0.0 | 5.57924E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.78225E-06 | 0 | 1.6019E-05 |
| H/R | None | None | 1.0 | N | 0.684 | 0.496 | 0.521601224155 | gnomAD-4.0.0 | 1.36889E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79928E-06 | 0 | 0 |
| H/Y | rs2052113416 |
None | 0.999 | N | 0.607 | 0.442 | 0.519568866481 | gnomAD-4.0.0 | 3.18518E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86002E-06 | 1.4332E-05 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.7286 | likely_pathogenic | 0.8938 | pathogenic | 0.188 | Stabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | I |
| H/C | 0.4097 | ambiguous | 0.6275 | pathogenic | 0.441 | Stabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | I |
| H/D | 0.7901 | likely_pathogenic | 0.9249 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.493634364 | None | None | I |
| H/E | 0.7533 | likely_pathogenic | 0.9152 | pathogenic | -0.059 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| H/F | 0.6019 | likely_pathogenic | 0.755 | pathogenic | 0.842 | Stabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| H/G | 0.7798 | likely_pathogenic | 0.9167 | pathogenic | -0.067 | Destabilizing | 0.999 | D | 0.664 | neutral | None | None | None | None | I |
| H/I | 0.8035 | likely_pathogenic | 0.925 | pathogenic | 0.832 | Stabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | I |
| H/K | 0.4337 | ambiguous | 0.6586 | pathogenic | 0.099 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | I |
| H/L | 0.3453 | ambiguous | 0.591 | pathogenic | 0.832 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | N | 0.479088986 | None | None | I |
| H/M | 0.7874 | likely_pathogenic | 0.8983 | pathogenic | 0.554 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| H/N | 0.3952 | ambiguous | 0.6082 | pathogenic | 0.006 | Stabilizing | 0.999 | D | 0.656 | neutral | N | 0.483860088 | None | None | I |
| H/P | 0.3719 | ambiguous | 0.624 | pathogenic | 0.641 | Stabilizing | 1.0 | D | 0.723 | prob.delet. | N | 0.490826133 | None | None | I |
| H/Q | 0.4004 | ambiguous | 0.637 | pathogenic | 0.101 | Stabilizing | 1.0 | D | 0.691 | prob.neutral | N | 0.475720607 | None | None | I |
| H/R | 0.1613 | likely_benign | 0.3169 | benign | -0.383 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | N | 0.43691429 | None | None | I |
| H/S | 0.655 | likely_pathogenic | 0.8378 | pathogenic | 0.061 | Stabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | I |
| H/T | 0.7364 | likely_pathogenic | 0.9037 | pathogenic | 0.18 | Stabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | I |
| H/V | 0.7102 | likely_pathogenic | 0.8781 | pathogenic | 0.641 | Stabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| H/W | 0.6298 | likely_pathogenic | 0.7446 | pathogenic | 0.829 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| H/Y | 0.2341 | likely_benign | 0.3949 | ambiguous | 1.07 | Stabilizing | 0.999 | D | 0.607 | neutral | N | 0.487940543 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.